Without limiting the scope of the invention, its background is described in connection with apoptosis. Apoptosis-(also called programmed cell death) plays a role in many diseases including developmental, tissue homeostasis, and degenerative diseases. Apoptosis is generally a directed process where the cell actively destroys itself in response to extracellular signals. Generally, apoptosis is characterized by the ordered cellular degradation of proteins and organelles, maintenance of plasma membrane integrity, and non-inflammatory phagocytosis of the cell.
Some types of cancer cells have been characterized by defects in the normal control of apoptosis. One example is the anti-apoptotic gene bcl-2. Enhanced expression of Bcl-2 provides resistance to apoptosis by suppressing the activation of the proapoptotic Bcl-2 related proteins Bax and Bak, which are essential in apoptosis initiated from both mitochondria and the endoplasmic reticulum. BH3 proteins are a member of the Bcl-2 family of protein with multidomain proapoptotic members Bax and Bak that release cytochrome c from mitochondria and kill cells. The BH3 domains capable of inducing oligomerization of to release cytochrome c. Bak as well as Bax, Bad, Bid and etc. are members of the pro-apoptotic proteins and known to have the BH3 domain to interact with anti-apoptotic Bcl proteins. (Adams, J. M.; Cory, S., Life-or-death decisions by the Bcl-2 protein family. Trends Biochem. Sci. 2001, 26, 61-66). These protein complexes like Bcl/Bak are a key element to regulate programmed cell death. Overexpression of the anti-apoptotic proteins Bcl-2 and Bcl-xL is commonly observed in human cancers.